Complex subtelomeric architectures in a complete rhesus macaque reference genome

Area of Science:

• Genomics
• Primate Biology
• Molecular Biology

Background:

• Telomere-to-telomere (T2T) genome assemblies provide complete sequences, crucial for understanding genome structure and function.
• Previous primate genome assemblies have been limited by challenges in resolving complex repetitive regions, particularly subtelomeric satellite arrays.
• The rhesus macaque is a vital model organism in biomedical research, necessitating a high-quality reference genome.

Purpose of the Study:

• To generate a near-perfect, telomere-to-telomere (T2T) genome assembly of the rhesus macaque (Macaca mulatta), named T2T-MMU8v2.0.
• To investigate and resolve the complex subtelomeric satellite-rich regions, identified as a major bottleneck in previous assembly efforts.
• To characterize the genomic architecture, repeat composition, and epigenetic features of these satellite arrays and their impact on gene content and regulation.

Main Methods:

• Employed an optimized assembly strategy utilizing long-read sequencing technologies.
• Focused on resolving approximately 8 megabase pairs (Mbp) of SATR satellite arrays.
• Discovered and characterized 268 previously unannotated repeat families within these regions.

Main Results:

• Achieved T2T-MMU8v2.0, a high base-level accuracy assembly of the rhesus macaque genome.
• Defined four distinct SATR genomic architectures with unique satellite compositions, segmental duplications, and epigenetic signatures, differing from hominid subtelomeric architectures.
• Identified 58 actively transcribed genes within these repetitive regions, suggesting gene innovation.
• Demonstrated improved alignment accuracy and chromatin accessibility detection using the new assembly.

Conclusions:

• T2T-MMU8v2.0 sets a new benchmark for primate genome assembly quality and completeness.
• The study highlights the functional and evolutionary significance of previously inaccessible genomic structures, particularly satellite arrays.
• This high-quality assembly will enhance future research in rhesus macaque population variation, regulatory element analysis, and comparative genomics.